The precise temporal and spatial control of molecules is a fundamental goal of both synthetic biology and nanotechnology, and is essential for building reliable nanoscale structures and devices. Nucleic acids, by virtue of their well-understood hybridization thermodynamics and kinetics, exponential information content and 0.4 nm addressability, and economy of synthesis and preparation, have emerged as a leading material for nanoscale engineering. (See, e.g., SantaLucia, J. & Hicks, D., Annu. Rev. Biochem. 2004, 33, 415-440; Bloomfield, V. A, et al., Nucleic Acids: Structures, Properties, and Functions, University Science Books: Sausalito, Calif., 2000; Carlson, R., Nat. Biotechnol. 2009, 27, 1091-1094; Aldaye, F. A., Science 2008, 321, 1795-1799; Shih, W. M. & Lin, C., Curr. Opin. Struct. Biol. 2010, 20, 276-282; Lu, Y. & Liu, J., Curr. Opin. Biotechnol. 2006, 17, 580-588; Willner, I., et al., Chem. Soc. Rev. 2008, 37, 1153-1165; Bath, J. & Turberfield, A. J., Nature Nanotechnol. 2007, 2, 275-284; and Zhang, D. Y. & Seelig, G., Nature Chem. 2010, DOI: 10.1038/NCHEM.957, the disclosures of each of which are incorporated herein by reference.) Furthermore, the biological relevance of nucleic acids and the ease of coupling nucleic acids to other materials, such as proteins and carbon nanotubes, facilitate the use of nucleic acids both as synthetic biomaterials and as scaffolds for other nanotechnological applications. (See, e.g., Bartel, D. P., Cell 2009, 136, 215-233; Lu, J., et al., Nature 2005, 435, 834-838; Rinker, S., et al, Nature Nanotechnol. 2008, 3, 418-422; Maune, H. T., et al., Nature Nanotechnol. 2010, 5, 61-66, the disclosures of each of which are incorporated herein by reference.)
Although the first generation of DNA nanotechnology research has focused on the self-assembly of static DNA nanostructures, recent works in the field have also expanded into the realm of constructing dynamic nucleic acid devices, in which nucleic acid nanostructures conditionally and programmably reconfigure in solution. (See, e.g., Bath, J. & Turberfield, A. J., Nature Nanotechnol. 2007, 2, 275-284; Zhang, D. Y. & Seelig, G., Nature Chem. 2010, 103-113; Winfree, E., et al., Nature 1998, 394, 539-544; Rothemund, P. W. K, et al., Plos Biol. 2004, 2, 2041-2053; Rothemund, P. W. K., Nature 2006, 440, 297-302; Douglas, S. M., et al., Nature 2009, 459, 414-418; and Zheng, J., et al., Nature 2009, 461, 74-77, the disclosures of each of which are incorporated herein by reference.) Examples include cascaded logical and amplification circuits, DNA origami boxes that close and open, molecular walkers that traverse predefined landscapes, controlled rotating DNA frameworks, and chain reaction DNA motors and dendrimers. (See, e.g., Stojanovic, M. N. & Stefanovic, D., Nat. Biotechnol. 2003, 21, 1069-1074; Lederman, H., et al., Biochemistry 2006, 45, 1194-1199; Win, M. N. & Smolke, C. D., Science 2008, 322, 456-460; Levy, M. & Ellington, A. D., Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 6416-6421; Seelig, G., et al., Science 2006, 314, 1585-1588; Seelig, G., et al., Am. Chem. Soc. 2006, 128, 12211-12220; Zhang, D. Y., et al., Science 2007, 318, 1121-1125; Frezza, B. M., et al., J. Am. Chem. Soc. 2007, 129, 14875-14879; Zhang, D. Y. & Winfree, E., J. Am. Chem. Soc. 2008, 130, 13921-13926; Andersen, E. S., et al., Nature 2009, 459, 73-76; Pei, R., et al., J. Am. Chem. Soc. 2006, 128, 12693-12699; Lund, K., et al., Nature 2010, 465, 206-210; Omabegho, T., et al., Science 2009, 324, 67-71; Green, S., et al., Phys. Rev. Lett. 2008, 101, 238101; Yurke, B., et al., Nature 2000, 406, 605-608; Yan, H., et al., Nature 2002, 415, 62-65; Gu, H., et al., Nature 2010, 465, 202-205; Dirks, R. M. & Pierce, N. A., Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 15275-1278; Venkataraman, S., et al., Nature Nanotechnol. 2007, 2, 490-494; and Yin, P., et al., Nature 2008, 451, 318-322, the disclosures of each of which are incorporated herein by reference.)
While some of the above constructions relied on functional nucleic acid molecules with innate catalytic activity (known as ribozymes and deoxyribozymes, see above citations), many others were constructed using purely rational design approaches, based on the well-characterized thermodynamic and kinetic properties of DNA hybridization, branch migration, and dissociation processes. (See, e.g., Dirks, R. M., et al., SIAM Rev. 2007, 49, 65-88; Zhang, D. Y. & Winfree, E., J. Am. Chem. Soc. 2009, 131, 17303-17314; and Yurke, B. & Mills, A. P., Genet. Programming Evolvable Machines 2003, 4, 111-122, the disclosures of each of which are incorporated herein by reference.) The latter group generally relies the clever and repeated use of a simple but reliable mechanism, known as toehold-mediated strand displacement, in which short, single-stranded domains on different DNA molecules hybridize to colocalize the molecules, enabling subsequent branch migration. (See, e.g., Zhang, D. Y. & Seelig, G., Nature Chem. 2010; and Yurke, B., et al., Nature 2000, cited above.) To further expand the scope of functions achievable with dynamic DNA nanotechnology, it is necessary to develop other molecular mechanisms that afford functionality that toehold-mediated strand displacement cannot achieve.